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<p>Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation of mature B lymphocytes in the blood, bone marrow, and lymph nodes. The development of chemotherapy resistance has increased the need for novel and less toxic therapeutic approaches. Owing to its unique biological properties, the anticancer potential of boric acid (BA) has attracted increasing attention. This study investigated the effects of BA on cell viability, apoptosis, and oxidative stress in HG-3 and MEC-1 CLL cell lines and evaluated its synergistic potential in combination with Venetoclax. Cell viability was assessed after 24 and 48&#xa0;h of treatment, and the IC₅₀ values of BA were determined as 75&#xa0;µg/mL for HG-3 cells and 80&#xa0;µg/mL for MEC-1 cells. Apoptosis was evaluated by measuring caspase-3 and caspase-8 activities, which were significantly increased in the combination groups compared with the control group (<i>p</i> &lt; 0.05). Oxidative stress was assessed using total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, molecular docking, molecular dynamics, reduced density gradient (RDG), and molecular electrostatic potential (MEP) analyses were performed to investigate the molecular interactions of BA. Taken together, these findings provide preliminary evidence supporting the biological activity of the BA–Venetoclax combination and justify further mechanistic and in vivo studies to evaluate its potential relevance in chronic lymphocytic leukemia.</p> Graphical Abstract <p></p>

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Boric Acid Combined with Venetoclax Induces Apoptosis in CLL Cell Lines via Caspase Activation and Oxidative Stress Modulation: In Vitro and In Silico Study

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Dilek Nur Bestil,
  • Hamdi Uysal

摘要

Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation of mature B lymphocytes in the blood, bone marrow, and lymph nodes. The development of chemotherapy resistance has increased the need for novel and less toxic therapeutic approaches. Owing to its unique biological properties, the anticancer potential of boric acid (BA) has attracted increasing attention. This study investigated the effects of BA on cell viability, apoptosis, and oxidative stress in HG-3 and MEC-1 CLL cell lines and evaluated its synergistic potential in combination with Venetoclax. Cell viability was assessed after 24 and 48 h of treatment, and the IC₅₀ values of BA were determined as 75 µg/mL for HG-3 cells and 80 µg/mL for MEC-1 cells. Apoptosis was evaluated by measuring caspase-3 and caspase-8 activities, which were significantly increased in the combination groups compared with the control group (p < 0.05). Oxidative stress was assessed using total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, molecular docking, molecular dynamics, reduced density gradient (RDG), and molecular electrostatic potential (MEP) analyses were performed to investigate the molecular interactions of BA. Taken together, these findings provide preliminary evidence supporting the biological activity of the BA–Venetoclax combination and justify further mechanistic and in vivo studies to evaluate its potential relevance in chronic lymphocytic leukemia.

Graphical Abstract